Comparative effects of the angiotensin II receptor blocker EXP 3174 and of the angiotensin-converting enzyme inhibitor captopril on renal glomerular hemodynamics in the dog.
The effects on glomerular hemodynamics of angiotensin-converting enzyme (ACE) inhibition with captopril and of angiotensin II receptor blockade with EXP 3174, an active metabolite of losartan, either alone or in combination, were compared in anesthetized dogs. Administration of EXP 3174 intrarenally led to an increase in renal blood flow by +14% and in glomerular filtration rate by +7%, thus decreasing the filtration fraction by -5%. Similar changes were observed at the single-nephron level. Water, sodium, potassium, and urea excretion rates rose considerably. A decrease in effective filtration pressure by -27% and an increase in ultrafiltration coefficient, Kf, by +57% were seen. A drop in total arteriolar resistance by -19% was mainly due to a decrease in efferent (-25%) rather than afferent (-14%) resistance. When captopril, an ACE inhibitor, was administered intravenously after and during EXP 3174, an additional increase in renal blood flow, by +8%, with no change in glomerular filtration rate was seen which led to an additional decrease in filtration fraction by -5%; additional increases were observed in water and urea but not in sodium and potassium excretion rates. An additional decrease in total arteriolar resistance, by -14%, was now evenly distributed between the efferent (-6%) and afferent (-8%) arterioles. Almost all of these additional changes disappeared when a bradykinin B2-antagonist, Hoe 140, was infused together with captopril. In conclusion, administration of an ACE inhibitor led to a significantly enhanced vasodilatory response in the kidney as compared with the administration of an angiotensin II-receptor blocker. This enhancement was almost eliminated by the coadministration of Hoe 140, thus rendering the participation of kinins fairly plausible.
Heller
J
J
Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Kramer
H J
HJ
Horácek
V
V
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000187:drug effects*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D004285:Dogs; D004338:Drug Combinations; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D019808:Losartan; D008297:Male; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*; D014508:Urea / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014867:Water / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D004338:Drug Combinations; D007093:Imidazoles; D013777:Tetrazoles; D014867:Water; D000804:Angiotensin II; C065679:icatibant; D014508:Urea; D002216:Captopril; D012964:Sodium; C066026:losartan carboxylic acid; D019808:Losartan; D011188:Potassium; D001920:Bradykinin